Nitric oxide induces hyperpolarization by opening ATP-sensitive K+ channels in guinea pig spiral modiolar artery

Jun Qiang Si, Hui Zhao, Yuqin Yang, Zhi-Gen Jiang, Alfred Nuttall

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Nitric oxide (NO) hyperpolarizes vascular smooth muscle cells and dilates blood vessels of various beds, but little is known on cochlear vasculatures. Using in vitro preparations of the spiral modiolar artery (SMA), intracellular electrical recording and labeling techniques, we found that the NO donor DPTA-NONOate (10 μM) caused a hyperpolarization of ∼9 mV in all the cells that had a low resting potential (RP) level near -40 mV. The hyperpolarization amplitude was concentration-dependent, with a 50% effect concentration (EC50) of 1 μM. The responses occur in both smooth muscle and endothelial cells, neither of which was blocked by 18β-glycyrrhetinic acid. The induced hyperpolarization was completely blocked by glipizide, but not by charybdotoxin, apamin, barium, 4-aminopyridine or tetraethylammonium. The hyperpolarizing responses were imitated by pinacidil (EC50=30 μM). The pinacidil-induced response was also blocked by glipizide but not by the other K+ channel blockers mentioned above. Both DPTA-NONOate and pinacidil had little membrane potential effect on cells that had a high RP level near -75 mV. However, when the high RP cells were depolarized to a level beyond -45 mV by barium, both DPTA-NONOate and pinacidil hyperpolarized these cells not differently from those that initially had a low RP. It is concluded that NO hyperpolarizes the SMA primarily by activating KATP channels in both muscle and endothelial cells.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalHearing Research
Volume171
Issue number1-2
DOIs
Publication statusPublished - Sep 2002

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Keywords

  • Cochlea
  • Endothelial cell
  • Membrane potential
  • Nitric oxide
  • Potassium channel
  • Smooth muscle cell
  • Spiral modiolar artery

ASJC Scopus subject areas

  • Sensory Systems

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